XIENCE 28 Global Study

Net Adverse Clinical Endpoint (NACE):

A composite rate of all-cause death, all myocardial infarction (modified Academic Research Consortium [ARC]), stent thrombosis (ARC definite or probable), stroke or major bleeding (Bleeding defined by the Bleeding Academic Research Consortium [BARC] type 2-5)

Net Adverse Clinical Endpoint (NACE):

A composite rate of all-cause death, all myocardial infarction (modified Academic Research Consortium [ARC]), stent thrombosis (ARC definite or probable), stroke or major bleeding (Bleeding defined by the Bleeding Academic Research Consortium [BARC] type 2-5)

Definite stent thrombosis:

Definite stent thrombosis is considered to have occurred by either angiographic or pathologic confirmation.

Probable stent thrombosis:

Clinical definition of probable stent thrombosis is considered to have occurred after intracoronary stenting in the following cases:

• Any unexplained death within the first 30 days
• Irrespective of the time after the index procedure, any MI that is related to documented acute ischemia in the territory of the implanted stent without angiographic confirmation of stent thrombosis and in the absence of any other obvious cause

Definite stent thrombosis:

Definite stent thrombosis is considered to have occurred by either angiographic or pathologic confirmation.

Probable stent thrombosis:

Clinical definition of probable stent thrombosis is considered to have occurred after intracoronary stenting in the following cases:

• Any unexplained death within the first 30 days
• Irrespective of the time after the index procedure, any MI that is related to documented acute ischemia in the territory of the implanted stent without angiographic confirmation of stent thrombosis and in the absence of any other obvious cause

Definite stent thrombosis:

Definite stent thrombosis is considered to have occurred by either angiographic or pathologic confirmation.

Probable stent thrombosis:

Clinical definition of probable stent thrombosis is considered to have occurred after intracoronary stenting in the following cases:

• Any unexplained death within the first 30 days
• Irrespective of the time after the index procedure, any MI that is related to documented acute ischemia in the territory of the implanted stent without angiographic confirmation of stent thrombosis and in the absence of any other obvious cause

All deaths are considered cardiac unless an unequivocal non-cardiac cause can be established. Specifically, any unexpected death even in patients with coexisting potentially fatal non-cardiac disease (e.g. cancer, infection) should be classified as cardiac.

Cardiac death: Any death due to proximate cardiac cause (e.g. MI, low-output failure, fatal arrhythmia), unwitnessed death and death of unknown cause, all procedure related deaths including those related to concomitant treatment.

Vascular death: Death due to non-coronary vascular causes such as cerebrovascular disease, pulmonary embolism, ruptured aortic aneurysm, dissecting aneurysm, or other vascular cause.

Non-cardiovascular death: Any death not covered by the above definitions such as death caused by infection, malignancy, sepsis, pulmonary causes, accident, suicide or trauma.

All deaths are considered cardiac unless an unequivocal non-cardiac cause can be established. Specifically, any unexpected death even in patients with coexisting potentially fatal non-cardiac disease (e.g. cancer, infection) should be classified as cardiac.

Cardiac death: Any death due to proximate cardiac cause (e.g. MI, low-output failure, fatal arrhythmia), unwitnessed death and death of unknown cause, all procedure related deaths including those related to concomitant treatment.

Vascular death: Death due to non-coronary vascular causes such as cerebrovascular disease, pulmonary embolism, ruptured aortic aneurysm, dissecting aneurysm, or other vascular cause.

Non-cardiovascular death: Any death not covered by the above definitions such as death caused by infection, malignancy, sepsis, pulmonary causes, accident, suicide or trauma.

All deaths are considered cardiac unless an unequivocal non-cardiac cause can be established. Specifically, any unexpected death even in patients with coexisting potentially fatal non-cardiac disease (e.g. cancer, infection) should be classified as cardiac.

Cardiac death: Any death due to proximate cardiac cause (e.g. MI, low-output failure, fatal arrhythmia), unwitnessed death and death of unknown cause, all procedure related deaths including those related to concomitant treatment.

Vascular death: Death due to non-coronary vascular causes such as cerebrovascular disease, pulmonary embolism, ruptured aortic aneurysm, dissecting aneurysm, or other vascular cause.

Non-cardiovascular death: Any death not covered by the above definitions such as death caused by infection, malignancy, sepsis, pulmonary causes, accident, suicide or trauma.

Patients present any of the following clinical or imaging evidence of ischemia:

• Clinical symptoms of ischemia;
• ECG changes indicative of new ischemia - new ST-T changes or new left bundle branch block (LBBB), development of pathological Q waves;
• Imaging evidence of a new loss of viable myocardium or a new regional wall motion abnormality)

AND confirmed with elevated cardiac biomarkers per ARC criteria:

• Periprocedural MI:
• Within 48h after PCI: CK-MB >3 x URL or Troponin > 3 x URL with baseline value < URL
• Within 72h after CABG: CK-MB >5 x URL or Troponin > 5 x URL with baseline value < URL
• Spontaneous MI (> 48h following PCI, > 72h following CABG): CK-MB > URL or Troponin > URL with baseline value < URL

Patients present any of the following clinical or imaging evidence of ischemia:

• Clinical symptoms of ischemia;
• ECG changes indicative of new ischemia - new ST-T changes or new left bundle branch block (LBBB), development of pathological Q waves;
• Imaging evidence of a new loss of viable myocardium or a new regional wall motion abnormality)

AND confirmed with elevated cardiac biomarkers per ARC criteria:

• Periprocedural MI:
• Within 48h after PCI: CK-MB >3 x URL or Troponin > 3 x URL with baseline value < URL
• Within 72h after CABG: CK-MB >5 x URL or Troponin > 5 x URL with baseline value < URL
• Spontaneous MI (> 48h following PCI, > 72h following CABG): CK-MB > URL or Troponin > URL with baseline value < URL

Patients present any of the following clinical or imaging evidence of ischemia:

• Clinical symptoms of ischemia;
• ECG changes indicative of new ischemia - new ST-T changes or new left bundle branch block (LBBB), development of pathological Q waves;
• Imaging evidence of a new loss of viable myocardium or a new regional wall motion abnormality)

AND confirmed with elevated cardiac biomarkers per ARC criteria:

• Periprocedural MI:
• Within 48h after PCI: CK-MB >3 x URL or Troponin > 3 x URL with baseline value < URL
• Within 72h after CABG: CK-MB >5 x URL or Troponin > 5 x URL with baseline value < URL
• Spontaneous MI (> 48h following PCI, > 72h following CABG): CK-MB > URL or Troponin > URL with baseline value < URL

Cardiac death:

Any death due to proximate cardiac cause (e.g. MI, low-output failure, fatal arrhythmia), unwitnessed death and death of unknown cause, all procedure related deaths including those related to concomitant treatment.

MI (Modified ARC):

Patients present any of the following clinical or imaging evidence of ischemia:

• Clinical symptoms of ischemia;
• ECG changes indicative of new ischemia - new ST-T changes or new left bundle branch block (LBBB), development of pathological Q waves;
• Imaging evidence of a new loss of viable myocardium or a new regional wall motion abnormality)

AND confirmed with elevated cardiac biomarkers per ARC criteria:

• Periprocedural MI:
• Within 48h after PCI: CK-MB >3 x URL or Troponin > 3 x URL with baseline value < URL
• Within 72h after CABG: CK-MB >5 x URL or Troponin > 5 x URL with baseline value < URL
• Spontaneous MI (> 48h following PCI, > 72h following CABG): CK-MB > URL or Troponin > URL with baseline value < URL

Cardiac death:

Any death due to proximate cardiac cause (e.g. MI, low-output failure, fatal arrhythmia), unwitnessed death and death of unknown cause, all procedure related deaths including those related to concomitant treatment.

MI (Modified ARC):

Patients present any of the following clinical or imaging evidence of ischemia:

• Clinical symptoms of ischemia;
• ECG changes indicative of new ischemia - new ST-T changes or new left bundle branch block (LBBB), development of pathological Q waves;
• Imaging evidence of a new loss of viable myocardium or a new regional wall motion abnormality)

AND confirmed with elevated cardiac biomarkers per ARC criteria:

• Periprocedural MI:
• Within 48h after PCI: CK-MB >3 x URL or Troponin > 3 x URL with baseline value < URL
• Within 72h after CABG: CK-MB >5 x URL or Troponin > 5 x URL with baseline value < URL
• Spontaneous MI (> 48h following PCI, > 72h following CABG): CK-MB > URL or Troponin > URL with baseline value < URL

Cardiac death:

Any death due to proximate cardiac cause (e.g. MI, low-output failure, fatal arrhythmia), unwitnessed death and death of unknown cause, all procedure related deaths including those related to concomitant treatment.

MI (Modified ARC):

Patients present any of the following clinical or imaging evidence of ischemia:

• Clinical symptoms of ischemia;
• ECG changes indicative of new ischemia - new ST-T changes or new left bundle branch block (LBBB), development of pathological Q waves;
• Imaging evidence of a new loss of viable myocardium or a new regional wall motion abnormality)

AND confirmed with elevated cardiac biomarkers per ARC criteria:

• Periprocedural MI:
• Within 48h after PCI: CK-MB >3 x URL or Troponin > 3 x URL with baseline value < URL
• Within 72h after CABG: CK-MB >5 x URL or Troponin > 5 x URL with baseline value < URL
• Spontaneous MI (> 48h following PCI, > 72h following CABG): CK-MB > URL or Troponin > URL with baseline value < URL

All death: All deaths are considered cardiac unless an unequivocal non-cardiac cause can be established. Specifically, any unexpected death even in patients with coexisting potentially fatal non-cardiac disease (e.g. cancer, infection) should be classified as cardiac.

MI (Modified ARC):

Patients present any of the following clinical or imaging evidence of ischemia:

• Clinical symptoms of ischemia;
• ECG changes indicative of new ischemia - new ST-T changes or new left bundle branch block (LBBB), development of pathological Q waves;
• Imaging evidence of a new loss of viable myocardium or a new regional wall motion abnormality)

AND confirmed with elevated cardiac biomarkers per ARC criteria:

• Periprocedural MI
• Spontaneous MI (> 48h following PCI, > 72h following CABG): CK-MB > URL or Troponin > URL with baseline value < URL

All death: All deaths are considered cardiac unless an unequivocal non-cardiac cause can be established. Specifically, any unexpected death even in patients with coexisting potentially fatal non-cardiac disease (e.g. cancer, infection) should be classified as cardiac.

MI (Modified ARC):

Patients present any of the following clinical or imaging evidence of ischemia:

• Clinical symptoms of ischemia;
• ECG changes indicative of new ischemia - new ST-T changes or new left bundle branch block (LBBB), development of pathological Q waves;
• Imaging evidence of a new loss of viable myocardium or a new regional wall motion abnormality)

AND confirmed with elevated cardiac biomarkers per ARC criteria:

• Periprocedural MI
• Spontaneous MI (> 48h following PCI, > 72h following CABG): CK-MB > URL or Troponin > URL with baseline value < URL

All death: All deaths are considered cardiac unless an unequivocal non-cardiac cause can be established. Specifically, any unexpected death even in patients with coexisting potentially fatal non-cardiac disease (e.g. cancer, infection) should be classified as cardiac.

MI (Modified ARC):

Patients present any of the following clinical or imaging evidence of ischemia:

• Clinical symptoms of ischemia;
• ECG changes indicative of new ischemia - new ST-T changes or new left bundle branch block (LBBB), development of pathological Q waves;
• Imaging evidence of a new loss of viable myocardium or a new regional wall motion abnormality)

AND confirmed with elevated cardiac biomarkers per ARC criteria:

• Periprocedural MI
• Spontaneous MI (> 48h following PCI, > 72h following CABG): CK-MB > URL or Troponin > URL with baseline value < URL

An acute symptomatic episode of neurological dysfunction attributed to a vascular cause lasting more than 24 hours or lasting 24 hours or less with a brain imaging study or autopsy showing new infarction.

• Ischemic Stroke: An acute symptomatic episode of focal cerebral, spinal, or retinal dysfunction caused by an infarction of central nervous system tissue.
• Hemorrhagic Stroke: An acute symptomatic episode of focal or global cerebral or spinal dysfunction caused by a non-traumatic intraparenchymal, intraventricular, or subarachnoid hemorrhage.
• Undetermined Stroke: A stroke with insufficient information to allow categorization as ischemic or hemorrhagic.
• Pharmacologic, i.e., thrombolytic drug administration, or Non-pharmacologic, i.e., neurointerventional procedure (e.g., intracranial angioplasty)

An acute symptomatic episode of neurological dysfunction attributed to a vascular cause lasting more than 24 hours or lasting 24 hours or less with a brain imaging study or autopsy showing new infarction.

• Ischemic Stroke: An acute symptomatic episode of focal cerebral, spinal, or retinal dysfunction caused by an infarction of central nervous system tissue.
• Hemorrhagic Stroke: An acute symptomatic episode of focal or global cerebral or spinal dysfunction caused by a non-traumatic intraparenchymal, intraventricular, or subarachnoid hemorrhage.
• Undetermined Stroke: A stroke with insufficient information to allow categorization as ischemic or hemorrhagic.
• Pharmacologic, i.e., thrombolytic drug administration, or Non-pharmacologic, i.e., neurointerventional procedure (e.g., intracranial angioplasty)

An acute symptomatic episode of neurological dysfunction attributed to a vascular cause lasting more than 24 hours or lasting 24 hours or less with a brain imaging study or autopsy showing new infarction.

• Ischemic Stroke: An acute symptomatic episode of focal cerebral, spinal, or retinal dysfunction caused by an infarction of central nervous system tissue.
• Hemorrhagic Stroke: An acute symptomatic episode of focal or global cerebral or spinal dysfunction caused by a non-traumatic intraparenchymal, intraventricular, or subarachnoid hemorrhage.
• Undetermined Stroke: A stroke with insufficient information to allow categorization as ischemic or hemorrhagic.
• Pharmacologic, i.e., thrombolytic drug administration, or Non-pharmacologic, i.e., neurointerventional procedure (e.g., intracranial angioplasty)

TLR is defined as any repeat percutaneous intervention of the target lesion (the treated segment from 5 mm proximal to the stent and to 5 mm distal to the stent) or bypass surgery of the target vessel performed for restenosis or other complication of the target lesion. All TLR should be classified prospectively as clinically indicated [CI] or not CI by the investigator prior to repeat angiography.

A revascularization is considered CI if angiography at follow-up shows a percent diameter stenosis ≥ 50% and if any one below occurs:

• A positive history of recurrent angina pectoris, presumably related to the target vessel;
• Objective signs of ischemia at rest (ECG changes) or during exercise test (or equivalent), presumably related to the target vessel;
• Abnormal results of any invasive functional diagnostic test (e.g: Doppler flow velocity reserve, fractional flow reserve);
• A TLR with a diameter stenosis ≥70% in the absence of the above mentioned ischemic signs or symptoms.

TLR is defined as any repeat percutaneous intervention of the target lesion (the treated segment from 5 mm proximal to the stent and to 5 mm distal to the stent) or bypass surgery of the target vessel performed for restenosis or other complication of the target lesion. All TLR should be classified prospectively as clinically indicated [CI] or not CI by the investigator prior to repeat angiography.

A revascularization is considered CI if angiography at follow-up shows a percent diameter stenosis ≥ 50% and if any one below occurs:

• A positive history of recurrent angina pectoris, presumably related to the target vessel;
• Objective signs of ischemia at rest (ECG changes) or during exercise test (or equivalent), presumably related to the target vessel;
• Abnormal results of any invasive functional diagnostic test (e.g: Doppler flow velocity reserve, fractional flow reserve);
• A TLR with a diameter stenosis ≥70% in the absence of the above mentioned ischemic signs or symptoms.

TLR is defined as any repeat percutaneous intervention of the target lesion (the treated segment from 5 mm proximal to the stent and to 5 mm distal to the stent) or bypass surgery of the target vessel performed for restenosis or other complication of the target lesion. All TLR should be classified prospectively as clinically indicated [CI] or not CI by the investigator prior to repeat angiography.

A revascularization is considered CI if angiography at follow-up shows a percent diameter stenosis ≥ 50% and if any one below occurs:

• A positive history of recurrent angina pectoris, presumably related to the target vessel;
• Objective signs of ischemia at rest (ECG changes) or during exercise test (or equivalent), presumably related to the target vessel;
• Abnormal results of any invasive functional diagnostic test (e.g: Doppler flow velocity reserve, fractional flow reserve);
• A TLR with a diameter stenosis ≥70% in the absence of the above mentioned ischemic signs or symptoms.

TVR is defined as any repeat percutaneous intervention or surgical bypass of any segment of the target vessel. The target vessel is defined as the entire major coronary vessel proximal and distal to the target lesion which includes upstream and downstream branches and the target lesion itself

A revascularization is considered clinically indicated if angiography at follow-up shows a percent diameter stenosis ≥ 50% and if one of the following occurs:

• A positive history of recurrent angina pectoris, presumably related to the target vessel;
• Objective signs of ischemia at rest (ECG changes) or during exercise test (or equivalent), presumably related to the target vessel;
• Abnormal results of any invasive functional diagnostic test (e.g., Doppler flow velocity reserve, fractional flow reserve);
• A TVR with a diameter stenosis ≥70% in the absence of the above mentioned ischemic signs or symptoms.

TVR is defined as any repeat percutaneous intervention or surgical bypass of any segment of the target vessel. The target vessel is defined as the entire major coronary vessel proximal and distal to the target lesion which includes upstream and downstream branches and the target lesion itself

A revascularization is considered clinically indicated if angiography at follow-up shows a percent diameter stenosis ≥ 50% and if one of the following occurs:

• A positive history of recurrent angina pectoris, presumably related to the target vessel;
• Objective signs of ischemia at rest (ECG changes) or during exercise test (or equivalent), presumably related to the target vessel;
• Abnormal results of any invasive functional diagnostic test (e.g., Doppler flow velocity reserve, fractional flow reserve);
• A TVR with a diameter stenosis ≥70% in the absence of the above mentioned ischemic signs or symptoms.

TVR is defined as any repeat percutaneous intervention or surgical bypass of any segment of the target vessel. The target vessel is defined as the entire major coronary vessel proximal and distal to the target lesion which includes upstream and downstream branches and the target lesion itself

A revascularization is considered clinically indicated if angiography at follow-up shows a percent diameter stenosis ≥ 50% and if one of the following occurs:

• A positive history of recurrent angina pectoris, presumably related to the target vessel;
• Objective signs of ischemia at rest (ECG changes) or during exercise test (or equivalent), presumably related to the target vessel;
• Abnormal results of any invasive functional diagnostic test (e.g., Doppler flow velocity reserve, fractional flow reserve);
• A TVR with a diameter stenosis ≥70% in the absence of the above mentioned ischemic signs or symptoms.

TLF is defined as a composite of all cardiac death, myocardial infarction attributed to target vessel or clinically-indicated TLR.

TLF is defined as a composite of all cardiac death, myocardial infarction attributed to target vessel or clinically-indicated TLR.

TLF is defined as a composite of all cardiac death, myocardial infarction attributed to target vessel or clinically-indicated TLR.

TVF is defined as a composite of cardiac death, MI attributed to target vessel, clinically-indicated TLR, or clinically-indicated TVR, non-TLR.

TVF is defined as a composite of cardiac death, MI attributed to target vessel, clinically-indicated TLR, or clinically-indicated TVR, non-TLR.

TVF is defined as a composite of cardiac death, MI attributed to target vessel, clinically-indicated TLR, or clinically-indicated TVR, non-TLR.

Bleeding per Bleeding Academic Research Consortium (BARC)definitions are as follows:

Type 0

Type 1

Type 2

Type 3

Type 4

Type 5

Where, Type 0 indicates no bleeding and type 5 indicates fatal bleeding.

Bleeding per Bleeding Academic Research Consortium (BARC)definitions are as follows:

Type 0

Type 1

Type 2

Type 3

Type 4

Type 5

Where, Type 0 indicates no bleeding and type 5 indicates fatal bleeding.

Bleeding per Bleeding Academic Research Consortium (BARC)definitions are as follows:

Type 0

Type 1

Type 2

Type 3

Type 4

Type 5

Where, Type 0 indicates no bleeding and type 5 indicates fatal bleeding.